Treatment and composition for achieving skin anti-aging benefits by corneum protease activation

ABSTRACT

Novel methods and compositions for treating aged and environmentally damaged skin are disclosed which provide improvements in the skin&#39;s visual appearance, function and clinical/biophysical properties by activating at least one proteolytic enzyme in the skin&#39;s stratum corneum. The disclosed treatment methods involve topical application of a novel cosmetic composition containing a combination of a cationic surfactant such as N,N,-dimethyldodecyl amine oxide (DMDAO), an anionic surfactant such as sodium dodecyl sulfate (SDS), or monoalkyl phosphate (MAP) and a chelating agent such as ethylene diamine tetraacetate (EDTA) to stimulate a chronic increase in the replacement rate of the skin&#39;s stratum corneum by means of corneum protease activation. This chronic, low level stimulation is effective to induce repair and replacement of the stratum corneum, epidermis, and dermis of the skin and improvements in the appearance, function, and anti-aging properties of the skin.

FIELD OF THE INVENTION

The present invention relates generally to a treatment method andcomposition for improving the skin's visual appearance, function, andclinical/biophysical properties which have been changed by factors suchas chronological age, chronic sun exposure, adverse environmentalpollutants, household chemicals, disease pathologies, smoking, andmalnutrition. In particular, the present invention relates to a methodof treating skin by increasing the skin's stratum corneum turnover ratethrough corneum protease activation. More particularly, the inventionrelates to the use of a combination of a cationic surfactant such asN,N,-dimethyldodecyl amine oxide (DMDAO), an anionic surfactant such assodium dodecyl sulfate (SDS), and a chelating agent such as ethylenediamine tetraacetate (EDTA) as additives to topically-applied cosmeticskincare products to treat and reduce the clinical and functional signsof aging and environmental damage in skin. The invention provides for aneffective alternative to the use of hydroxy acids and retinoid compoundsto treat aged and environmentally-damaged skin.

BACKGROUND OF THE INVENTION

With chronological age and chronic exposure to adverse environmentalfactors, the visual appearance, physical properties, and physiologicalfunctions of skin change in ways that are considered cosmeticallyundesirable. The most notable and obvious changes include thedevelopment of fine lines and wrinkles, loss of elasticity, increasedsagging, loss of firmness, loss of color evenness (tone), coarse surfacetexture, and mottled pigmentation. Less obvious, but measurable changeswhich occur as skin ages or endures chronic environmental insult includea general reduction in cellular and tissue vitality, reduction in cellreplication rates, reduced cutaneous blood flow, reduced moisturecontent, accumulated errors in structure and function, and a reductionin the skin's ability to remodel and repair itself. Many of the abovealterations in appearance and function are caused by changes in theouter epidermal layer of the skin, while others are caused by changes inthe lower dermis. Regardless of the stimulus for skin damage, whendamage occurs, numerous natural and complex biochemical mechanisms areset into motion in attempts to repair the damage.

When the epidermis is injured, the epidermal basal cells respond to theinjury by dividing at a more frequent rate. This increase in replicationrate results in a more rapid replacement of the damaged epidermis with anew epidermis and stratum corneum, a process referred to as “epidermalcell renewal.” Common examples of injuries which can increase epidermalcell renewal rates include abrasion, chemical damage, pH extremes,excessive sun exposure, or allergic or non-allergic contact irritation.If the injury is too severe, the increased replication will result in a“hyperplastic” epidermis and a thickened, poorly-functioning stratumcorneum which is manifested as dry, rough scales. Other common stimuliwhich induce epidermal cell renewal include physical removal of thestratum corneum (i.e., an example of which is tape stripping, a processwhere tape is applied to the skin and pulled off, removing the top layerof the stratum corneum with it) and friction (i.e., on the soles andheels of the feet), all processes which result in epidermal hyperplasia.Hydroxy acids and retinoids also induce epidermal hyperplasia atappropriate concentrations, although the mechanisms appear to bedifferent. It is believed by many that hydroxy acids exert their effectsby inducing physical exfoliation of the corneum, whereas the retinoidsmore likely work by interacting with cytoplasmic and nuclear bindingreceptors to alter gene expression. Schiltz, J. et al. “Retinoic acidinduces cyclic changes in epidermal thickness and dermal collagen andglycosaminoglycan biosynthesis rates,” J. Invest. Dermatol. 87:663-667(1986), describe various effects of retinoic acid on epidermal anddermal biology including cyclical epidermal thickening and hyperplasia,and dermal changes in the rates of biosynthesis of collagen andglycosaminoglycans.

With chronological age and chronic environmental exposure (notably UVA,UVB, and IR radiation), the dermis undergoes changes in structure andfunction which result in many of the characteristics of aged skin,including loss of elasticity, formation of wrinkles, loss ofwater-holding capacity, sagging, and poor microcirculation. At themolecular level, these changes have been correlated with biochemicalchanges in the content and structure of the extracellular matrix towhich the major cells of the dermis (i.e., the fibroblasts) reside.Collagen becomes highly cross-linked and inelastic, elastin is reducedin amounts and is incorrectly distributed, and the glycosaminoglycansbecome reduced in amounts, which results in reduced intercellular water.

As a result of this changed architecture, the normal amounts anddistribution of trace metal ions, growth factors, hormones, andcytokines becomes altered which causes the fibroblasts to becomemetabolically less active or quiescent. Although these cells havenatural mechanisms to repair themselves and the matrix in which theyreside, with age and too much damage, they are less able to repair thedamage, and the condition continues to deteriorate. If the quiescentfibroblasts can be metabolically activated and stimulated to divide,they will synthesize new extracellular matrix and the old, damagedmatrix will be enzymatically degraded and replaced. This process ofbalanced synthesis and degradation is referred to as “dermalremodeling.” The activation process can be accomplished in manydifferent ways, including chemical stimulation by selected hormones,growth factors, cytokines, vitamins, botanical extracts and retinoids,or by increasing the nutrient supply (i.e., blood flow) to the tissue.

Although the mechanisms are not completely understood, it appears thatphysical or chemical changes to the intact stratum corneum of the skinwill result in epidermal basal cell replication and subsequent increasesin epidermal cell renewal. If the injury stimulus is too great, the skinwill be unable to correct the damage or will “over-respond” in such away as to cause extensive epidermal hyperplasia and dry, flaky,poorly-differentiated stratum corneum. If the damage stimulus is lessand is well controlled, the process of epidermal replacement shouldresult in a healthier, better-functioning epidermis and in a stratumcorneum which looks and feels better, has greater capacity to holdmoisture, and has fewer surface fine lines.

It is known that damage to the stratum corneum not only sets into motionnatural biochemical mechanisms to repair and replace the epidermis, butdisturbances in the corneum also stimulate repair and remodeling of thedermis. U.S. Pat. No. 5,720,963 to Smith (“the '963 patent”) teachesthat chronic and significant disruption of the skin's water barrierusing a combination of cerebrosides, hydroxy acids, and retinoids causeschronic injury to the corneum and results in epidermal and dermal repairof the structurally-deteriorated skin if the disruption is maintainedfor a sufficient period of time. The mechanisms by which the combinationof materials used in the '963 patent cause increased epidermal cellrenewal and chronic skin repair are entirely different from those whichare involved in the current invention. Although the end benefits to theskin are similar, the '963 patent teaches that water barrier disruptionagents such as cerebrosides or organic solvents or detergents, incombination with retinoids or hydroxy acids will disrupt the corneumwater barrier and stimulate basal cell replication rates. The Applicanthas discovered that chronic stimulation of the normal process ofdesquamation by activation of at least one endogenous corneum proteasewill result in increased epidermal turnover and epidermal and dermalremodeling. This is not a chronic injury; instead, it is an increase inthe rates of corneum shedding by one of the natural mechanisms; theincreased desquamation stimulates the natural mechanisms involved inreplacing the lost corneum, a process which results in beneficial skinremodeling.

In a series of peer-reviewed scientific publications, Lundstrom, A. andEgelrud, T. “Cell Shedding from Human Plantar Skin In Vitro: Evidence ofits Dependence on Endogenous Proteolysis,” J. Invest. Dermatol.91:340-343 (1988); Egelrud, T. and Lundstrom, A., “The Dependence ofDetergent-Induced Cell Dissociation in Non-Palmo-Plantar Stratum Corneumon Endogenous Proteolysis,” J. Invest. Dermatol. 95: 456-459 (1990);Lundstrom, A. and Egelrud, T. “Stratum Corneum Chymotryptic Enzyme: AProteinase which may be Generally Present in the Stratum Corneum andwith a Possible Involvement in Desquamation,” Acta Dermato-Venereol71:471-474 (1991); investigators from the Department of Dermatology,University Hospital, Umea, Sweden, demonstrated that human stratumcorneum possesses endogenous chymotryptic proteinase enzyme(s) which canbe activated in vitro by a combination of the cationic surfactantN,N,-dimethyldodecyl amine oxide (DMDAO), the anionic surfactant sodiumdodecyl sulfate (SDS), and the chelating agent ethylene diaminetetraacetate (EDTA). Activation of these enzymes resulted in theseparation of individual corneum cells (i.e. corneocytes), a processwhich Egelrud's group has proposed mimics the natural desquamationprocess. The Egelrud group have described the role of the endogenouschymotryptic proteinase enzyme(s) to be important in naturaldesquamation of the skin, but their work did not predict that stratumcorneum protease activation would enhance the rates of epidermal cellrenewal and set up natural epidermal and dermal biochemical mechanismswhich could provide benefit to aged or environmentally-damaged skin.

Prior art physiological, chemical, or mechanical methods of increasingstratum corneum renewal rates to achieve benefit such as hydroxy acids,retinoids, barrier disrupters, tape stripping, solvent extraction, etc.all have various drawbacks, such as significant irritation to the skin,skin toxicity, the requirement of high concentrations of expensiveingredients, or of low pH. In addition, all these methods involve theinvocation of damage to the skin, which sets up repair mechanisms. Formost of these treatments, there will be a period of time, up to severalweeks or months, during which the skin becomes irritated and after whichtolerance sets in and the symptoms of irritation may decrease and/orcease. When using the method described in the present invention, thesedrawbacks are not encountered.

Applicant has surprisingly discovered a method of treatment andcomposition for aged and environmentally damaged skin that enhances thestratum corneum turnover rate by activation of at least one endogenousproteinase. The treatment, which results in skin with improved visualappearance, function, and clinical/biophysical properties, is not knownin the prior art. Moreover, the novel method of treatment andcompositions of the present invention accomplish this at lowconcentrations, at a neutral pH, in all the vehicles in which theactives have been tested, and without causing clinical irritation orchronic damage to the skin.

SUMMARY OF THE INVENTION

The features of the invention may be realized and attained by means ofthe instrumentalities and combinations particularly pointed out in theappended claims. Further features of the invention will be set forth inpart in the description which follows and in part will be apparent fromthe description, or may be learned by practice of the invention.

In accordance with the purpose of the invention in one of its aspectsembodied and broadly described herein, there is disclosed a method oftreating skin comprising topical application to aged or damaged skin ofa cosmetic composition comprising a chemically compatible combination ofone or more surfactants and at least one chelating agent, in an amounteffective to provide chronic stimulation of the skin's stratum corneumturnover rate, and a reduction in the stratum corneum turnover time, byactivating one or more of the skin's endogenous corneum proteaseenzymes. In another aspect, the present invention includes a cosmetictreatment composition for aged or damaged skin comprising a chemicallycompatible combination of one or more surfactants and at least onechelating agent, in an amount effective to provide chronic stimulationof the skin's stratum corneum turnover rate, and a reduction in thestratum corneum turnover time, by activating one or more of the skin'sendogenous corneum protease enzymes.

Additional aspects of the invention will be set forth in part in thedescription which follows, and in part will be apparent from thedescription, or may be learned by practice of the invention. Thepurposes and features of the invention will be realized and attained bymeans of the elements and combinations particularly pointed out in theappended claims.

DETAILED DESCRIPTION

The present invention provides a novel method of treatment and a novelcomposition for treating aged and environmentally damaged ordeteriorated skin. The present invention provides a method of treatingskin comprising topical application to damaged skin of a cosmeticcomposition in an amount effective to provide a chronic, increasedreplacement rate of the skin's stratum corneum by means of corneumprotease activation, wherein the increased replacement rate is effectiveto induce repair, replacement, and remodeling of the stratum corneum,epidermis, and dermis of the skin and improvements in the appearance,function, and aging properties of the skin.

According to the present invention, “increased replacement rate” and“stimulation of the skin's stratum corneum turnover rate” includes anyrate of stratum corneum or epidermal turnover which is greater than thatof the untreated skin on the same site of the same individual.Typically, this increase in turnover rate, or reduction in turnovertime, can range from about 1% to about 40%. Preferably turnover rate isincreased by about 25%. There are many different ways in which epidermisand stratum corneum turnover rate can be measured, including but notrestricted to assays to measure dansyl chloride disappearance, dihydroxyacetone staining disappearance, or use of radioactive thymidine tomeasure basal cell labeling index. Chronic stimulation of the stratumcorneum turnover rate refers to the repeated, or constant stimulationoccurring with regular treatment of the skin with the composition of thepresent invention.

Similarly, “reduction in skin's stratum corneum turnover time” is theresulting decrease in the time needed for the shedding of the skinlayer. The turnover time reduction can range from about 1% to about 40%,preferably the time reduction is about 25%.

“Corneum protease activation” refers to a stimulation, above that ofuntreated skin, of one or more of the endogenous stratum corneumchymotryptic protease enzymes believed to be involved in the naturaldesquamation process of corneocyte shedding and subsequent stratumcorneum turnover.

The effectiveness of the method of the present invention in providingskin anti-aging benefits can be measured by a number of ways. Each ofthese strategies for evaluating the effectiveness of the invention canbe used independently or together by one skilled in the art. The methodis effective when it decreases stratum corneum turnover time by fromabout 1% to about 40%, preferably by at least about 25%. It is alsoeffective when it reduces TEWL by from about 0% to about 100%,preferably by at least about 1%. It is further effective when itdecreases canthus skin roughness by from about 1% to about 60%,preferably by at least about 9%. The method is effective when itdecreases the number of wrinkles on the canthus by from about 1% toabout 60%, preferably by at least about 9%. It is also effective when itincreases skin moisture on the canthus by from about 1% to about 90%,preferably by at least about 21%. It is effective when it increases skinmoisture on the cheek by from about 1% to about 90%, preferably by atleast about 14%.

The cosmetic composition should be topically applied regularly towhatever skin area requires treatment with the frequency and in theamount necessary to achieve the desired results. Preferably, thecosmetic composition is applied at least once per day, most preferablytwice per day. The frequency of treatment depends on the degree ofdamage or deterioration of the skin, the responsiveness of the user'sskin, the strength of the active ingredients in the cosmetic product,the effectiveness of the vehicle used to deliver the active ingredientsinto the stratum corneum, the ease with which the formula is removed byphysical contact with clothing or it's removal by sweat or otherintrinsic or extrinsic fluids, and the convenience to the user'slifestyle. Typical concentrations of relatively simple biochemicallyactive substances such as the novel treatment composition describedherein can range from about 0.01% to about 5.0% by weight based on thetotal weight of the cosmetic composition, and the formula should beapplied to the skin at a rate equal to from about 1.0 mg/cm² of skin toabout 20.0 mg/cm² of skin. Preferably, the formula should contain fromabout 0.39% to about 0.78% by weight based on the total weight of thecosmetic composition. Most preferably, the formula should contain about0.78% active ingredients and be applied to the skin at a rate of about5.0 mg/cm² of skin.

The cosmetic composition of the present invention comprises safe andeffective amounts of one or more surfactants and at least one chelatingagent. Use of these combinations of materials will result in anactivation of one or more of the resident stratum corneum proteasechymotryptic enzymes, which causes a loss of adherence betweencorneocytes, thus allowing them to be shed at a faster rate. While themechanism or mechanisms of this activation process are unknown, wespeculate that the surfactants could cause one or more of the followingchanges, including conformational changes in the enzyme, uncovering ofthe active site of the enzyme, or removal of lipids or other adherentsubstances from the enzyme. The chelating agent could somehow regulatethe concentration of a metal cation which may be required for activitysuch as Ca⁺⁺, Mg⁺⁺, Sr⁺⁺, or Mn⁺⁺. The surfactants can be selected fromany natural or synthetic surfactants suitable for use in cosmeticcompositions and can be cationic, anionic, zwitterionic, non-ionic, ormixtures thereof. (See Rosen, M., “Surfactants and InterfacialPhenomena,” Second Edition, John Wiley & Sons, New York, 1988, Chapter1, pages 4-31). Suitable cationic surfactants can include, but are notlimited to DMDAO or other amine oxides, long-chain primary amines,diamines and polyamines and their salts, quaternary ammonium salts,polyoxyethylenated long-chain amines, and quaternized polyoxyethylenatedlong-chain amines. Suitable anionic surfactants can include, but are notlimited to SDS, salts of carboxylic acids (i.e. soaps), salts ofsulfonic acids, salts of sulfuric acid, phosphoric and polyphosphoricacid esters, alkylphosphates, monoalkyl phosphate (MAP), and salts ofperfluorocarboxylic acids.

Suitable zwitterionic surfactants can include but are not limited tococoamidopropyl hydroxysultaine (CAPHS) and others which arepH-sensitive and require special care in designing the appropriate pH ofthe formula (i.e. alkylaminopropionic acids, imidazoline carboxylates,and betaines) or those which are not pH-sensitive (i.e. sulfobetaines,sultaines). Suitable non-ionic surfactants can include but are notlimited to alkylphenol ethoxylates, alcohol ethoxylates,polyoxyethylenated polyoxypropylene glycols, polyoxyethylenatedmercaptans, long-chain carboxylic acid esters, alkonolamides, tertiaryacetylenic glycols, polyoxyethylenated silicones, N-alkylpyrrolidones,and alkylpolyglycosidases. Any combination of surfactants is acceptable.Preferably, the surfactant includes at least one anionic and onecationic surfactant, or at least one cationic and one zwitterionicsurfactant which are compatible, e.g., do not form complexes whichprecipitate appreciably when mixed. Most preferably, the surfactantincludes DMDAO and SDS, or DMDAO and MAP. Applicants believe that SDSand MAP are interchangeable in the present invention.

The chelating agent can be any chelating agent suitable for use in acosmetic composition. Suitable chelating agents can include, but are notlimited to any natural or synthetic chemical which has the ability tobind divalent cationic metals such as Ca⁺⁺, Mn⁺⁺, or Mg⁺⁺. Preferably,the chelating agent is selected from EDTA, disodium EDTA, EGTA, citricacid, or dicarboxylic acids. Most preferably, the chelating agent isEDTA.

Where the cosmetic composition contains a cationic surfactant such asDMDAO, the percent of such surfactant in the composition is from about0.01% to about 5.0% by weight based on the total weight of the cosmeticcomposition, preferably from about 0.18% to about 0.36% and mostpreferably about 0.36%. Where the cosmetic composition contains ananionic surfactant such as SDS or MAP, the percent of such surfactant inthe composition is from about 0.01% to about 5.0% by weight based on thetotal weight of the cosmetic composition, preferably from about 0.06% toabout 0.12% and most preferably about 0.12%. The cosmetic compositionincludes a chelating agent such as EDTA at from about 0.01% to about5.0% by weight based on the total weight of the cosmetic composition,preferably from about 0.15% to about 0.30% and most preferably about0.30%.

While various combinations of surfactant and chelating agents may beused, the cosmetic composition of the present invention most preferablyincludes a combination of DMDAO/SDS/EDTA, alternatively the sameconcentration of MAP can substitute for the SDS. In the context of thepresent invention, a preferred composition is 0.18% DMDAO, 0.06% SDS and0.15% EDTA by weight based on the total weight of the cosmeticcomposition. This composition has been designated as a IX concentrationof the active ingredients. Concentration levels for this combination canrange from between about 0.1× to about 10×, preferably from about 1× toabout 3× and most preferably about 2×. The present invention providesaged or environmentally-damaged skin with anti-aging benefits which arecomparable to those achieved with hydroxy acids and retinoids.Furthermore, the indicated combinations of DMDAO/SDS/EDTA are non-toxic,and non-irritating. In this context, “non-toxic” means that thesematerials, at the recommended concentrations and usage rates, do notdamage living skin cells and “non-irritating” means that there are noperiods of time during their use when these materials cause classicalclinical irritation characterized by immunological reactions and/orburning, itching, stinging, erythema, or scaling of the skin. In markedcontrast, efficacious levels of retinoids and hydroxy acids can causethe skin to experience all of these symptoms of irritation during theinitial stages of treatment, and can persist indefinitely.

The indicated combinations of DMDAO/SDS/EDTA are effective in allsuitable cosmetic vehicles, including emulsions, creams, lotions,solutions (both aqueous and hydro-alcoholic), anhydrous bases (such aslipsticks and powders), gels, and ointments. One skilled in the artwould generally recognize these and other standard cosmetic vehiclesthat can be used in the present invention. Thus, the present inventionmay be formulated with a variety of cosmetic vehicles in addition tothose described in the Examples below. Variations and other appropriatevehicles will be apparent to the skilled artisan and are appropriate foruse in the present invention. Preferably, the cosmetic vehicle isselected from oil-in-water emulsions, hydro-alcoholic solutions, andencapsulated beads in anhydrous systems. Most preferably, the vehicle isan oil-in-water emulsion. Such emulsions and their compositions andmethods of making are well known in the art. It is important, however,that the concentrations and combinations of the surfactants andchelating agents be selected in such a way that the combinations arechemically compatible and do not form complexes which precipitate fromthe finished product.

The composition of the present invention can be used in many cosmeticproducts including, but not limited to, moisturizing cream, skin benefitcreams and lotions, gels, ointments, foundation, night cream, lipstick,cleansers, toners, masks, and color cosmetic products. The compositionis most preferably used in anti-aging products for the face and otherbody parts, most especially leave-on products.

Products according to the present invention in which humectantproperties are desired may include amino acids, chondroitin sulfate,diglycerin, erythritol, fructose, glucose, glycerin, glycerol, glycol,1,2,6-hexanetriol, honey, hyaluronic acid, hydrogenated honey,hydrogenated starch hydrolysate, inositol, lactitol, maltitol, maltose,mannitol, natural moisturization factor, PEG-15 butanediol, polyglycerylsorbitol, salts of pyrollidone carboxylic acid, potassium PCA, propyleneglycol, sodium glucuronate, sodium PCA, sorbitol, sucrose, trehalose,urea, and xylitol.

Products according to the present invention in which antioxidantproperties are desired may include acetyl cysteine, ascorbic acid,ascorbic acid polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanolpectinate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butylhydroquinone, cysteine, cysteine HCl, diamylhydroquinone,di-t-butylhydroquinone, dicetyl thiodipropionate, dioleyl tocopherylmethylsilanol, disodium ascorbyl sulfate, distearyl thiodipropionate,ditridecyl thiodipropionate, dodecyl gallate, erythorbic acid, esters ofascorbic acid, ethyl ferulate, ferulic acid, gallic acid esters,hydroquinone, isooctyl thioglycolate, kojic acid, magnesium ascorbate,magnesium ascorbyl phosphate, methylsilanol ascorbate, natural botanicalanti-oxidants such as green tea or grape seed extracts,nordihydroguaiaretic acid, octyl gallate, phenylthioglycolic acid,potassium ascorbyl tocopheryl phosphate, potassium sulfite, propylgallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite,sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxidedismutase, sodium thioglycolate, sorbityl furfural, thiodiglycol,thiodiglycolamide, thiodiglycolic acid, thioglycolic acid, thiolacticacid, thiosalicylic acid, tocophereth-5, tocophereth-10, tocophereth-12,tocophereth-18, tocophereth-50, tocopherol, tocophersolan, tocopherylacetate, tocopheryl linoleate, tocopheryl nicotinate, tocopherylsuccinate, and tris(nonylphenyl)phosphite.

Products according to the present invention in which moisturizingproperties are desired may include acetylated lanolin, acetylatedlanolin alcohol, acrylates/C10-30 alkyl acrylate crosspolymer, acrylatescopolymer, alanine, algae extract, aloe barbadensis, aloe barbadensisextract, aloe barbadensis gel, althea officinalis extract, aluminumstarch octenylsuccinate, aluminum stearate, apricot (prunus armeniaca)kernel oil, arginine, arginine aspartate, arnica montana extract,ascorbic acid, ascorbyl palmitate, aspartic acid, avocado (perseagratissima) oil, barium sulfate, barrier sphingolipids, butyl alcohol,beeswax, behenyl alcohol, beta-sitosterol, BHT, birch (betula alba) barkextract, borage (borago officinalis) extract,2-bromo-2-nitropropane-1,3-diol, butcherbroom (ruscus aculeatus)extract, butylene glycol, calendula officinalis extract, calendulaofficinalis oil, candelilla (euphorbia cerifera) wax, canola oil,caprylic/capric triglyceride, cardamon (elettaria cardamomum) oil,carnauba (copernicia cerifera) wax, carrageenan (chondrus crispus),carrot (daucus carota sativa) oil, castor (ricinus communis) oil,ceramides, ceresin, ceteareth-5, ceteareth-12, ceteareth-20, cetearyloctanoate, ceteth-20, ceteth-24, cetyl acetate, cetyl octanoate, cetylpalmitate, chamomile (anthemis nobilis) oil, cholesterol, cholesterolesters, cholesteryl hydroxystearate, citric acid, clary (salvia sclarea)oil, cocoa (theobroma cacao) butter, coco-caprylate/caprate, coconut(cocos nucifera) oil, collagen, collagen amino acids, corn (zea mays)oil, fatty acids, decyl oleate, dextrin, diazolidinyl urea, dimethiconecopolyol, dimethiconol, dioctyl adipate, dioctyl succinate,dipentaerythrityl hexacaprylate/hexacaprate, DMDM hydantoin, DNA,erythritol, ethoxydiglycol, ethyl linoleate, eucalyptus globulus oil,evening primrose (oenothera biennis) oil, fatty acids, tructose,gelatin, geranium maculatum oil, glucosamine, glucose glutamate,glutamic acid, glycereth-26, glycerin, glycerol, glyceryl distearate,glyceryl hydroxystearate, glyceryl laurate, glyceryl linoleate, glycerylmyristate, glyceryl oleate, glyceryl stearate, glyceryl stearate SE,glycine, glycol stearate, glycol stearate SE, glycosaminoglycans, grape(vitis vinifera) seed oil, hazel (corylus americana) nut oil, hazel(corylus avellana) nut oil, hexylene glycol, honey, hyaluronic acid,hybrid safflower (carthamus tinctorius) oil, hydrogenated castor oil,hydrogenated coco-glycerides, hydrogenated coconut oil, hydrogenatedlanolin, hydrogenated lecithin, hydrogenated palm glyceride,hydrogenated palm kernel oil, hydrogenated soybean oil, hydrogenatedtallow glyceride, hydrogenated vegetable oil, hydrolyzed collagen,hydrolyzed elastin, hydrolyzed glycosaminoglycans, hydrolyzed keratin,hydrolyzed soy protein, hydroxylated lanolin, hydroxyproline,imidazolidinyl urea, iodopropynyl butylcarbamate, isocetyl stearate,isocetyl stearoyl stearate, isodecyl oleate, isopropyl isostearate,isopropyl lanolate, isopropyl myristate, isopropyl palmitate, isopropylstearate, isostearamide DEA, isostearic acid, isostearyl lactate,isostearyl neopentanoate, jasmine (jasminum officinale) oil, jojoba(buxus chinensis) oil, kelp, kukui (aleurites moluccana) nut oil,lactamide MEA, laneth-16, laneth-10 acetate, lanolin, lanolin acid,lanolin alcohol, lanolin oil, lanolin wax, lavender (lavandulaangustifolia) oil, lecithin, lemon (citrus medica limonum) oil, linoleicacid, linolenic acid, macadamia ternifolia nut oil, magnesium stearate,magnesium sulfate, maltitol, matricaria (chamomilla recutita) oil,methyl glucose sesquistearate, methylsilanol PCA, microcrystalline wax,mineral oil, mink oil, mortierella oil, myristyl lactate, myristylmyristate, myristyl propionate, neopentyl glycol dicaprylate/dicaprate,octyldodecanol, octyldodecyl myristate, octyldodecyl stearoyl stearate,octyl hydroxystearate, octyl palmitate, octyl salicylate, octylstearate, oleic acid, olive (olea europaea) oil, orange (citrusaurantium dulcis) oil, palm (elaeis guineensis) oil, palmitic acid,pantethine, panthenol, panthenyl ethyl ether, paraffin, PCA, peach(prunus persica) kernel oil, peanut (arachis hypogaea) oil, PEG-8 C12-18ester, PEG-15 cocamine, PEG-150 distearate, PEG-60 glyceryl isostearate,PEG-5 glyceryl stearate, PEG-30 glyceryl stearate, PEG-7 hydrogenatedcastor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castoroil, PEG-20 methyl glucose sesquistearate, PEG-40 sorbitan peroleate,PEG-5 soy sterol, PEG-10 soy sterol, PEG-2 stearate, PEG-8 stearate,PEG-20 stearate, PEG-32 stearate, PEG-40 stearate, PEG-50 stearate,PEG-100 stearate, PEG-150 stearate, pentadecalactone, peppermint (menthapiperita) oil, petrolatum, phospholipids, polyamino sugar condensate,polyglyceryl-3 diisostearate, polyquarternium-24, polysorbate 20,polysorbate 40, polysorbate 60, polysorbate 80, polysorbate 85,potassium myristate, potassium palmitate, potassium sorbate, potassiumstearate, propylene glycol, propylene glycol dicaprylate/dicaprate,propylene glycol dioctanoate, propylene glycol dipelargonate, propyleneglycol laurate, propylene glycol stearate, propylene glycol stearate SE,PVP, pyridoxine dipalmitate, quaternium-15, quaternium-18 hectorite,quaternium-22, retinol, retinyl palmitate, rice (oryza sativa) bran oil,RNA, rosemary (rosmarinus officinalis) oil, rose oil, safflower(carthamus tinctorius) oil, sage (salvia officinalis) oil, salicylicacid, sandalwood (santalum album) oil, serine, serum protein, sesame(sesamum indicum) oil, shea butter (butyrospermum parkii), silk powder,sodium chondroitin sulfate, sodium DNA, sodium hyaluronate, sodiumlactate, sodium palmitate, sodium PCA, sodium polyglutamate, sodiumstearate, soluble collagen, sorbic acid, sorbitan laurate, sorbitanoleate, sorbitan palmitate, sorbitan sesquioleate, sorbitan stearate,sorbitol, soybean (glycine soja) oil, sphingolipids, squalane, squalene,stearamide MEA-stearate, stearic acid, stearoxy dimethicone,stearoxytrimethylsilane, stearyl alcohol, stearyl glycyrrhetinate,stearyl heptanoate, stearyl stearate, sunflower (helianthus annuus) seedoil, sweet almond (prunus amygdalus dulcis) oil, synthetic beeswax,tocopherol, tocopheryl acetate, tocopheryl linoleate, tribehenin,tridecyl neopentanoate, tridecyl stearate, triethanolamine, tristearin,urea, vegetable oil, water, waxes, wheat (triticum vulgare) germ oil,and ylang ylang (cananga odorata) oil.

Products according to the present invention in which ultraviolet light(UVA and UVB) absorbing properties are desired may include benzophenone,benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-4,benzophenone-5, benzophenone-6, benzophenone-7, benzophenone-8,benzophenone-9, benzophenone-10, benzophenone-11, benzophenone-12,benzyl salicylate, butyl PABA, cinnamate esters, cinoxate,DEA-methoxycinnamate, diisopropyl methyl cinnamate, ethyldihydroxypropyl PABA, ethyl diisopropylcin namate, ethylmethoxycinnamate, ethyl PABA, ethyl urocanate, glyceryl octanoatedimethoxycinnamate, glyceryl PABA, glycol salicylate, homosalate,isoamyl p-methoxycinnamate, PABA, PABA esters, Parsol 1789, andisopropylbenzyl salicylate.

Additional skin care preparation ingredients include skin lighteningagents (e.g. kojic acid, hydroquinine, ascorbic acid and derivatives,retinoids, etc.), hydroxy acids (e.g. lactic acid, salicylic acid,etc.), emollients (e.g. esters, fatty acids, etc.), vitamins (i.e. A, C,E, K, etc.), trace metals (e.g. zinc, calcium, selenium, etc.),anti-irritants (e.g. steroids, non-steroidal anti-inflammatories, etc.),antimicrobial agents (e.g. triclosan, etc.), botanical extracts (e.g.aloe vera, chamomile, cucumber extract, ginkgo bibloba, ginseng,rosemary, etc.), dyes and color ingredients (e.g. D&C blue no. 4, D&Cgreen is no. 5, D&C orange no. 4, D&C red no. 17, D&C red no. 33, D&Cviolet no. 2, D&C yellow no. 10, D&C yellow no. 11, DEA-cetylphosphate), preservatives (e.g. BHA), emollients (i.e. organic esters,fatty acids, lanolin and its derivatives, plant and animal oils andfats, di- and triglycerides, etc.), antiirritants (i.e., steroids,nonsteroidal antiinflammatories, glycyrrhizates, etc.), antimicrobialagents (i.e., triclosan, ethanol, etc.), and fragrances (natural andartificial).

One skilled in the art will understand that the terms “mixture” and“mixing” in this patent are used in the broad sense of the words, withthe term “mixing” including, but not limited to, stirring, blending,dispersing, milling, homogenizing, and other similar methods.

The cosmetic composition of the present invention is effective at pHvalues between about 2.5 and about 10.0. Preferably, the pH of thecomposition is between the following pH ranges: about 5.5 and about 8.5,about 5 to about 10, about 5 to about 9, about 5 to about 8, about 3 toabout 10, about 3 to about 9, about 3 to about 8, and about 3 to about8.5. Most preferably, the pH is about 8. One of ordinary skill in theart may add appropriate pH adjusting ingredients to the compositions ofthe present invention to adjust the pH to an acceptable range.

EXAMPLES

Three main types of experiments were performed to screen the potentialfor formulas to provide anti-aging benefits to skin. These were (1)stratum corneum transit time, as measured by the rate of loss of skincolor following treatment with dihydroxy acetone, (2) barrier integrity,as measured by temporary trans-epidermal water loss (TEWL) followingovernight treatment with occlusive patches containing the test material,and (3) tests for actual facial skin benefit, including measurements ofskin moisture on the face, long term TEWL, skin firmness, number ofwrinkles around the canthus (the corner of the eye), texture (roughness)of the canthus skin, skin scales, and expert grading evaluations.

Stratum Corneum Turnover Studies

Example 1

The following procedure was used to estimate corneum transit time. Asmany as different sites per forearm were marked using a plastictemplate, and baseline readings of color intensity were determined usinga Minolta chromameter (b* value). Occlusive Hilltop chambers (2 cmdiameter) containing 0.02 ml Mary Kay Sun Essentials® Sunless TanningLotion product with dihydroxy acetone (“DHA”) were placed on the sites.After 6 hours, these patches were removed, and 18 hours later, the colorintensity was again determined using the chromameter; the delta b (Δb)values were calculated as the difference between the reading and thebaseline. Panelists themselves applied the products to the brown spotsin the morning and evening during the ensuing 10 days, and chromameterreadings were repeated after 3, 5, 7, and 10 days. The color decay slopewas calculated as the percent loss per day, and the transit timedetermined by extrapolating to 100% loss of color.

The activity of the DSE is not dependent on the vehicle, as long as thevehicle is a suitable carrier of the DSE components to the surface ofthe skin. For the experiments to be described, five different vehicleswere used, which are referred to as vehicles A, B, C, D, and E. VehicleA is a simple non-moisturizing, non-drying oil-in-water emulsion (75%water) which is routinely used to dissolve hydrophobic or hydrophilicingredients for testing on the skin. Vehicle B is a proprietary,oil-in-water emulsion (62% water) which contains UVA and UVB sunscreens(SPF 15). Vehicle C is a proprietary non-ionic, highly-moisturizingoil-in-water emulsion (61% water). Vehicle D is a proprietary, anhydrousformula which contains DSE incorporated into porous Nylon 12 particles(final formula <5% water). Vehicle E is a proprietary,highly-moisturizing oil-in-water emulsion (57% water).

Table 1 shows the effects of 0.18% DMDAO+0.06% SDS+0.15% EDTA on humanstratum corneum turnover rates (i.e. transit time), as determined by theDHA disappearance on forearm skin. Vehicle A is a control, oil-in-water,non-drying, non-moisturizing emulsion developed as a vehicle to test forthe effects of materials on skin.

As shown in Table 1, whereas the transit time was 13.0 days for VehicleA alone, addition of 0.18% DMDAO+0.06% SDS+0.15% EDTA reduced thetransit time to 7.8 days, which represents a 40.0% reduction (p=0.030).The number of panelists=11. The difference between the two treatments,as determined by paired Student t tests, was statistically significantat the 97% confidence level.

While U.S. Pat. No. 5,720,963 teaches that the use of a surfactant, suchas sodium lauryl sulfate, alone can provide benefit to aged skin, themechanism by which the benefit occurs is totally different in thepresent invention. The benefit in U.S. Pat. No. 5,720,963 depends onchronic disruption of the stratum corneum barrier, which is an unnaturalevent; caused by the partial removal and/or disruption of the specialmolecular packing of the intercorneocyte lipids by surfactants. Thiscauses injury and damage to the skin. That patent also teaches thatchronic barrier disruption can be achieved by the insertion of“abnormal” cerebrosides into the lipid lamellae structures, or by thecreation of a thick, scaly layer or stratum corneum by stimulating rapiddivision of epidermal basal cells with Vitamin A palmitate.

In contrast, the mechanism of the present invention involves activationof the natural mechanism for desquamation (i.e., activation of aprotease enzyme), which results in stimulation of epidermal cellrenewal. The combination of ingredients in the composition of thepresent invention does not cause damage to the skin because theconcentrations that are used are lower than the critical micelleconcentration of the surfactants.

As seen with other agents such as retinoids and hydroxy acids, it can beexpected that a reduction in corneum transit time will provide skin withanti-aging benefits. The term “anti-aging benefits” as used herein meansany reversal of the physical or functional changes which occur in skinas a result of intrinsic (i.e. natural) aging as caused by the passageof time, or environmentally-induced changes due to sun, weatherconditions, or exposure to adverse chemical substances. Examples ofbenefits include, but are not limited to improvements in the following:fine lines and wrinkles, uneven pigmentation, excessive dryness,excessive roughness, fragility, corneum water holding capacity,microcirculation, elasticity, firmness, epidermal turnover rates, anddermal water content. TABLE 1 Corneum Turnover % Reduction in TreatmentTime (Days) Turnover Time Vehicle A 13.0 — Vehicle A + 7.8 40.0DMDAO/SDS/EDTA

Example 2

The same procedure as in Example 1 was followed for preparing sites,applying products and evaluating transit time. Table 2 shows the effectsof once per day vs twice per day application of 0.18% DMDAO+0.06%SDS+0.15% EDTA in Vehicle B on human stratum corneum turnover rates, asdetermined by DHA disappearance on forearm skin. Vehicle B is asunscreen formula.

Once per day application of the formula (e.g., in the morning) reducedthe transit time by 24.8% compared to the untreated control sites(p=0.045), and twice per day application of the formula (e.g., morningand evening) reduced the transit time 34.9% (p==0.005). Thus,twice-a-day application of a topical product containing the inventivecomposition will provide more anti-aging benefit than if the product isused only once per day. Number of panelists=10. TABLE 2 Corneum Turnover% Reduction in Treatment Time (Days) Turnover Time No Treatment 10.9 —Vehicle B + 8.2 24.8 DMDAO/SDS/EDTA Morning Application Only Vehicle B +7.1 34.9 DMDAO/SDS/EDTA Morning and Evening Application

Example 3

The same procedure as in Example 1 was followed for preparing sites,applying products and evaluating transit time. Experiments wereperformed to assess the effects of DMDAO/SDS/EDTA concentration and pHon corneum turnover rates as determined by the DHA disappearance onforearm skin. The indicated materials were formulated into Vehicle A. A1× concentration=0.18% DMDAO, 0.06% SDS, and 0.15% EDTA, at theindicated pH; a 2× concentration is double these concentrations. Numberof panelists=10. The results as shown in Table 3 clearly demonstratethat there does exist a DMDAO/SDS/EDTA concentration-dependence, withthe higher concentration giving higher increases in turnover rates atall pH values. Furthermore, the increased pH gave higher values. Thus,as expected for an enzyme-mediated effect, the effects wereconcentration- and pH-dependent. TABLE 3 Corneum Turnover % Reduction inTreatment Time (Days) Turnover Time No Treatment 18.9 — 1×DMDAO/SDS/EDTA, pH 5 15.0 20.6 2× DMDAO/SDS/EDTA, pH 5 14.0 25.9 1×DMDAO/SDS/EDTA, pH 6.5 14.9 21.2 2× DMDAO/SDS/EDTA, pH 6.5 14.8 21.7 1×DMDAO/SDS/EDTA, pH 8.0 13.1 30.7 2× DMDAO/SDS/EDTA, pH 8.0 12.3 34.9

Example 4

The same procedure as in Example 1 was followed for preparing sites,applying products, and evaluating stratum corneum transit time. Thisexperiment was performed to assess the effects of DMDAO/SDS/EDTA whenformulated into Vehicle D, a proprietary anhydrous formula in which theDSE was incorporated into porous Nylon 12 particles, which were thenadded to the formula. The concentration of DSE in this formula was 2×,and the product was applied twice per day. Number of panelists=12. TABLE4 Corneum Turnover % Reduction in Treatment Time (Days) Turnover Time NoTreatment 14.8 — Vehicle D 14.0 5.4 Vehicle D + 2× 10.8 27.4DMDAO/SDS/EDTA

As shown in Table 4, whereas the transit time was 14.8 days for theuntreated sites, Vehicle D alone did not reduce the transit time to astatistically significant level. Addition of 2×DMDAO/SDS/EDTA to VehicleD reduced the transit time to 10.8 days, which represents a 27.4%reduction.

Example 5

The same procedure as in Example 1 was followed for preparing sites,applying products, and evaluating stratum corneum transit time. Thisexperiment was performed to assess the effects of substituting adifferent surfactant for SDS in the DMDAO/SDS/EDTA. The vehicle for thisexperiment was Vehicle E, which is a proprietary, highly-moisturizingoil-in-water emulsion. Four different formulas were prepared, all usingVehicle E as the base. While DMDAO and EDTA were included at 1×concentrations in all four formulas, the SDS was substituted withequimolar concentrations of either an amphoteric surfactant(cocoamidopropyl hydroxy-sultaine), or an anionic surfactant (C₉-C₁₅monoalkyl phosphate). The products were applied twice per day, and thenumber of panelists=20. TABLE 5 Corneum Turnover % Reduction inTreatment Time (Days) Turnover Time No Treatment 19.3 — Vehicle E +DMDAO + sodium 17.2 10.5 dodecyl sulfate + EDTA Vehicle E + DMDAO + 19.9−3.3 cocoamphodiacetate + EDTA Vehicle E + DMDAO + decyl 18.4 4.3polyglucose + EDTA Vehicle E + DMDAO + 17.8 7.3 cocoamidopropylhydroxysultaine + EDTA Vehicle E + DMDAO + monoalkyl 17.5 9.0phosphate + EDTA

As shown in Table 5, the combination of DMDAO+SDS+EDTA reduced thecorneum transit time 10.5% (p vs no treatment=0.031). Substitution ofthe zwitterionic surfactant cocoamidopropyl hydroxysultaine for SDSsimilarly reduced transit time (7.3% reduction, p vs no treatment=0.045)as did the anionic surfactant monoalkyl phosphate (9.0% reduction, p vsno treatment=0.017). In contrast, the amphoteric surfactantcocoamphodiacetate did not reduce transit time (−3.3% reduction, p vs notreatment=0.348). Similarly, the non-ionic surfactant decyl polyglucosedid not reduce transit time (4.3% reduction, p vs no treatment=0.451).There were no statistical differences between the formula containing SDSand cocoamidopropyl hydroxysultaine (p=0.209) or monoalkyl phosphate(MAP) (p=0.253). In conclusion, while an other anionic surfactant (MAP)and a zwitterionic surfactant (cocoamidopropyl hydroxysultaine, whichhas anionic character at the pH tested) substituted for SDS in thisinvention, the amphoteric or nonionic surfactants (cocoamphodiacetateand decyl polyglucose) that were tested did not substitute for the SDS.

Barrier Impact Study

Example 6

Corneum protease activation is believed to result in corneocytedyshesion and an increase in the rate of stratum corneum turnover.Because water loss through the stratum corneum occurs by passage throughthe intercorneal lipid lamellar structures, trans-epidermal water loss(“TEWL”) measurements were employed to screen for barrier “loosening”.An experiment was performed to assess the acute (i.e., short term)effects of DMDAO/SDS/EDTA concentrations and formula pH on TEWL. Testinginvolved application of the formulas overnight under occlusive skinpatches. The forearms of human subjects were patched overnight with theindicated formulas, the patches were removed, and TEWL was measured 6hours later using a ServoMed evaporimeter. The data are presented as %increased TEWL compared to the pre-patch baseline values. The indicatedmaterials were formulated into Vehicle A. A 1× concentration=0.18%DMDAO, 0.06% SDS, and 0.15. % EDTA, at the indicated pH; a 2×concentration is double these concentrations. Number of panelists=10.

The data, shown in Table 6, clearly demonstrate that when using thisacute occlusive test protocol, there was a DSE concentration-dependence,with the higher concentration giving marginal increases in TEWL at allpH values. TABLE 6 % Increased TEWL Treatment vs Baseline Vehicle A, pH5 9.9 1× DMDAO/SDS/EDTA, pH 5 14.7 2× DMDAO/SDS/EDTA, pH 5 15.1 VehicleA, pH 6.5 17.7 1× DMDAO/SDS/EDTA, pH 6.5 18.8 2× DMDAO/SDS/EDTA, pH 6.521.0 Vehicle A, pH 8.0 7.3 1× DMDAO/SDS/EDTA, pH 8.0 22.7 2×DMDAO/SDS/EDTA, pH 8.0 23.7Chronic Efficacy Studies

Example 7

The effects of the combination of 0.18% DMDAO, 0.06% SDS, and 0.15% EDTAin Vehicle B were tested for actual facial skin benefit. After takingbaseline measurements, panelists applied the product to their face twiceper day for a 28-day period, after which the measurements were againtaken. Skin moisture was determined using the Nova Dermal Phase Meter(impedance), TEWL using the ServoMed evaporimeter, firmness using theCutometer 474 (R0 value), number of wrinkles on the canthus by imageanalysis of Silflo replicas, and canthus texture/roughness using imageanalysis of Silflo replicas (Ra value). The product was not applied onthe morning for which the measurements were taken. Number ofpanelists=9. From Table 7 it can be clearly seen that this compositionincreased skin moisture on the face, improved the water barrier (i.e.reduced TEWL), increased firmness, improved the texture of the canthusskin, and reduced the number of wrinkles around the canthus. It isnoteworthy that while the immediate effects of the DMDAO/SDS/EDTAcombination, when applied in occlusive patches overnight, loosens thecorneum and results in increased TEWL (Table 6), the long-term effectsof topical application of the inventive formula to the skin results inthe formation of a better-functioning, healthier corneum which providesa better barrier as measured by reduced water loss from the skin. Thisfurther supports the conclusion that the mechanisms by which theinventive DMDAO/SDS/EDTA combination operates differently from prior artmechanisms, which chronically increase TEWL. A chronic increase in TEWLrepresent chronic skin damage, which causes the skin to repair itself.TABLE 7 % Improvement p values Skin Benefit from Baseline vs BaselineMoisture (Canthus) 21.6 0.001 Moisture (Cheek) 14.5 0.003 TEWL(Cheek)(Reduced) 10.8 0.028 Firmness (Cheek), R0 11.1 0.103 Roughness,Canthus, Ra 9.9 0.012 # Wrinkles, Canthus 9.8 0.007

Another chronic study was performed to illustrate the beneficial effectson the face of a combination of 0.18% DMDAO, 0.06% SDS, and 0.15%disodium EDTA in Vehicle C. Vehicle C is a moisturizing formula.

After baseline measurements were taken, 13 human volunteers applied theproduct to their face twice per day (morning and evening). The productwas not applied on the morning for which the measurements were taken. Inaddition to the measurements described for the experiment in Table 7, anexpert graded the severity of the canthus fine lines and wrinkles(modified Packman scoring system) and D'Squames were taken on the cheek.The D'Squames test (Cuderm Corp., Dallas, Tex.) evaluates skin conditionby applying tape to the skin and pulling it off (tape stripping). Thequality and amount skin adhering to the tape is then determined bycomputer-aided image analysis. This technique is well known in the artof measuring skin condition. The D'Squames were evaluated for fine andcoarse flakes. The resulting improvements in facial skin after a 28-daytreatment period are shown in Table 8. The results clearly showstatistically-significant improvements in terms of facial moisture,increased stratum corneum barrier integrity (i.e., reduced TEWL),increased elasticity, decreased wrinkles and fine lines, and decreasedscales. TABLE 8 % Improvement p value SKIN BENEFIT from Baseline vsBaseline Moisture (Canthus) 30.8 0.00 Moisture (Cheek) 26.7 0.00 TEWL(Cheek) (Reduced) 36.1 0.00 Canthus Wrinkles (Expert Grading) 39.6 0.00Canthus Wrinkles (Replicas) 11.7 0.03 D'Squames (Cheek Scales) 77.2 0.02Elasticity (Cheek) 13.4 0.01

Example 8

Longer term clinical benefits of the composition of the presentinvention have also been evaluated. Thirty panelists applied products (acombination cleanser/mask/toner and a moisturizer) to their skin as partof their regular morning and evening skincare routine. These productsincluded a total 2.84× concentration of the active ingredients of theinvention, with MAP substituted for SDS.

The panelists were monitored for skin improvement at the beginning ofthe study, and at 2, 4, 6, and 8 weeks. They were evaluated for face andneck moisture, dryness, surface fine lines, canthus wrinkles, firmness,smoothness, softness, clarity, neck texture, skin barrier, skinbrightness, and evenness of tone.

Face and neck moisture were evaluated using impedance measurements, anelectrical conductivity measurement using the Nova Dermal Phase Meter.Dryness, surface fine lines, smoothness, softness, skin brightness, andevenness of tone were determined by an expert grader using a calibratedvisual analog scale from 1 to 10. Skin smoothness and softness wereevaluated using tactile observations by the grader. Surface fine lineswere both counted and the severity of the lines evaluated generallyaccording to the Packman-Gans method, J. Soc. Cosmetic Chem. 29:70(1978), using weighted scoring. Dryness, skin brightness, and evennessof tone were evaluated using a calibrated visual analog scale from 1 to10.

Firmness was evaluated using a Hargens ballistometer, a device thatevaluates the elasticity and firmness of the skin by dropping a smallbody onto the skin and recording its first two rebound peaks. Asfirmness and elasticity decrease the second peak will be smaller incomparison to the first. Clarity was evaluated using a MinoltaChromameter, which measures the total light reflected from the skincompared to the amount of red and brown/yellow light. These measurementsare mathematically analyzed to determine the clarity of the skin.

Skin Barrier or TEWL (trans epidermal water loss) is measured using aServo Madr Register Evaporimeter EP1, which uses a probe to measurewater vapor as it leaves the skin. Canthus wrinkles and neck texturewere evaluated by comparing the skin to silicone replicas (negativeimpressions) made of the individuals' skin at baseline. Thepost-treatment silicone replicas were evaluated by computer imageanalysis to determine the number and depth of the wrinkles compared topretreatment replicas.

As shown in Table 9, continued improvement was seen for the vastmajority of skin condition parameters throughout the 8 weeks of thestudy. The small increase in skin barrier was not statisticallysignificant. TABLE 9 % Improvement from Baseline Benefit 2 Weeks 4 Weeks6 Weeks 8 Weeks Face Moisture 18.1 27.1 30.8 39.9 Neck Moisture 14.230.1 36.2 43.3 Dryness 28.1 33.7 39.2 50.8 Surface Fine Lines 17.5 20.828.6 34.7 Canthus Wrinkles 11.7 22.3 29.5 36.5 Firmness 10.7 17.3 18.324.6 Smoothness 26.4 38.6 50.7 64.1 Softness 30.4 63.2 82.0 98.6 Clarity3.8 6.7 7.2 7.9 Neck Texture 3.7 8.6 14.7 28.3 Skin Barrier 0.8 3.1 3.94.2 Skin Brightness 5.7 12.6 20.3 26.1 Evenness of Tone 6.1 16.1 18.026.1

While illustrative embodiments of the invention have been describedabove and are attached, it is, of course, understood that variousmodifications will be apparent to those of ordinary skill in the art.

1-41. (canceled)
 42. A cosmetic skin care composition comprising: (i)magnesium ascorbyl phosphate; (ii) citrus medica limonum oil; and (iii)cucumber extract, Wherein the compositing is formulated for topicalapplication to skin.
 43. The composition of claim 42, wherein thecomposition is an emulsion.
 44. The composition of claim 42, wherein thecomposition is a cream, a lotion, a gel, or an ointment.
 45. Thecomposition of claim 42, wherein the composition is a solution.
 46. Thecomposition of claim 42, wherein the composition is an anhydrous base.47. The composition of claim 42, further comprising a surfactant and achelating agent.
 48. The composition of claim 47, wherein thecomposition comprises a cationic surfactant and an anionic surfactant.49. The composition of claim 48, wherein the cationic surfactant isN,N,-dimethyldodecyl amine oxide.
 50. The composition of claim 48,wherein the anionic surfactant is sodium dodecyl sulfate or monoalkylphosphate.
 51. The composition of claim 48, wherein the chelating agentis ethylene diamine tetraacetate.
 52. The composition of claim 42,wherein the composition is a skin lightening composition.
 53. A methodof treating skin comprising topically applying the composition of claim42 to the skin.
 54. The method of claim 53, wherein the composition isan emulsion.
 55. The method of claim 53, wherein the composition is acream, a lotion, a gel, or an ointment.
 56. The method of claim 53,wherein the composition is a solution.
 57. The method of claim 53,wherein the composition is an anhydrous base.
 58. The method of claim53, wherein the composition further comprises a surfactant and achelating agent.
 59. The method of claim 58, wherein the compositioncomprises a cationic surfactant and an anionic surfactant.
 60. Themethod of claim 59, wherein the cationic surfactant isN,N,-dimethyldodecyl amine oxide.
 61. The method of claim 59, whereinthe anionic surfactant is sodium dodecyl sulfate or monoalkyl phosphate.62. The method of claim 59, wherein the chelating agent is ethylenediamine tetraacetate.
 63. The method of claim 53, wherein thecomposition lightens the skin.